Wang H, Marsters S A, Baker T, Chan B, Lee W P, Fu L, Tumas D, Yan M, Dixit V M, Ashkenazi A, Grewal I S
Department of Immunology, Genentech Inc. South San Francisco, CA 94080, USA.
Nat Immunol. 2001 Jul;2(7):632-7. doi: 10.1038/89782.
Interactions of the tumor necrosis factor superfamily members B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) with their receptors-transmembrane activator and CAML interactor (TACI) and B cell maturation molecule (BCMA)-on B cells play an important role in the humoral immune response. Whereas BCMA is restricted to B cells, TACI is also expressed on activated T cells; we show here that TACI-Fc blocks the activation of T cells in vitro and inhibits antigen-specific T cell activation and priming in vivo. In a mouse model for rheumatoid arthritis (RA), an autoimmune disease that involves both B and T cell components, TACI-Fc treatment substantially inhibited inflammation, bone and cartilage destruction and disease development. Thus, BLyS and/or APRIL are important not only for B cell function but for T cell-mediated immune responses. Inhibition of these ligands might have therapeutic benefits for autoimmune diseases, such as RA, that involve both B and T cells.
肿瘤坏死因子超家族成员B淋巴细胞刺激因子（BLyS）和增殖诱导配体（APRIL）与其受体——跨膜激活剂和CAML相互作用分子（TACI）以及B细胞成熟分子（BCMA）——在B细胞上的相互作用在体液免疫反应中起重要作用。虽然BCMA仅限于B细胞表达，但TACI在活化的T细胞上也有表达；我们在此表明，TACI-Fc在体外可阻断T细胞的活化，并在体内抑制抗原特异性T细胞的活化和启动。在类风湿性关节炎（RA）的小鼠模型中，一种涉及B细胞和T细胞成分的自身免疫性疾病，TACI-Fc治疗可显著抑制炎症、骨和软骨破坏以及疾病发展。因此，BLyS和/或APRIL不仅对B细胞功能很重要，对T细胞介导的免疫反应也很重要。抑制这些配体可能对涉及B细胞和T细胞的自身免疫性疾病（如RA）具有治疗益处。
